Cytomorphology of metastatic malignant peripheral nerve sheath tumour present in pleural fluid: Case study and literature review.

The cytomorphology of MPNST in effusion specimens is rarely described. In this paper, the detailed cytopathological and immunohistochemical characteristics of metastatic MPNST has been described in pleural effusion. Patients' medical history and the judicious utilization of ancillary studies contribute to ensure precise cytological diagnoses. The cytomorphology of malignant peripheral nerve sheath tumour (MPNST) in effusion specimens can be diagnostically challenging. The author presents detailed cytopathological and immunohistochemical characteristics of a case of metastatic MPNST in pleural effusion.

Wogonin inhibits hepatoma cell proliferation by targeting miR-27b-5p/YWHAZ axis.

Wogonin (5,7-dihydroxy-8-methoxyflavone), a natural flavonoid compound in herbal plants, can suppress growth in hepatocellular carcinoma (HCC). However, the microRNA (miRNA) expression profiles that are influenced by wogonin have not been thoroughly described. To explore the novel miRNAs and the biological mechanism underlying the effect of wogonin on HCC cells. The effect of wogonin on Huh7 cell growth was assessed both in vitro and in vivo. The expression profiles of miRNAs were obtained by small RNA sequencing. Luciferase reporter experiment and bioinformatics analysis were conducted to determine whether tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ) can bind to miR-27b-5p. Effects of the ectopic expression of YWHAZ and miR-27b-5p on Huh7 cells proliferation and apoptosis were evaluated. Furthermore, the cell cycle, apoptosis and multiple signaling pathway-related molecules were detected by Western blot analysis. Wogonin substantially inhibited the growth of Huh7 cells both in vitro and in vivo. Seventy miRNAs exhibited greater than twofold changes in wogonin-treated cells. Upregulation of miR-27b-5p inhibited Huh7 cell proliferation, and the anticancer effect of wogonin was reversed after miR-27b-5p knockdown. miR-27b-5p directly targeted YWHAZ in HCC cells. The proliferation-inhibiting effect of miR-27b-5p was revoked by YWHAZ overexpression. Meanwhile, inhibition of HCC growth was achieved by downregulating YWHAZ. Wogonin exerted antitumor activity through multiple signaling molecules, such as focal adhesion kinase, protein kinase B, mammalian target of rapamycin and molecules related to apoptosis and cell cycle by upregulating miR-27b-5p and downregulating YWHAZ. Our findings suggest that miR-27b-5p/YWHAZ axis contributes to the inhibitory effect of wogonin in HCC by targeting related genes and multiple signaling pathways.

Preliminary studies on intimal injury related to stent retrieval in a canine model.

OBJECTIVE: This pilot study aimed to observe intimal injuries related to stent retrieval in the iliac artery of a canine. BACKGROUND: In-stent restenosis remains challenging owing to permanent stent implantation. A retrievable stent may be alternative for intervention without permanent residue. METHODS: Five retrievable stents with point-to-point overlapped double-layer scaffolds were deployed into the iliac arteries and retrieved on days 14, 21, 28, 35, and 42 from five canines. RESULTS: Arterial diameter decreased by 9-10% before retrieval and 15% on day 14 after retrieval. In the 14-day-stent, the stent surface was clean without visible fibrin. In the 28-day-stent, the overlay was mainly composed of fibrin and fibroblasts. The proliferation of smooth muscle cells has not yet been observed with α-smooth muscle actin staining. In the 42-day-stent, endothelial and smooth muscle cells decreased under the struts, and the internal elastic lamina was interrupted segmentally. Neointima formation involves fibroblasts and smooth muscle cells. Neointimal thickness was negatively correlated with strut space. Stent traces on the artery wall tended to be flat at a follow-up14 days after retrieval. The primary intima was completely covered by neointima. Two stents could not be retrieved because of in-stent thrombosis or capture loss. CONCLUSIONS: The stent was covered mainly by depositional fibrin after 28 days and by typical neointima after 42 days. The stent retrieval procedure did not induce injury to vascular smooth muscle, and the intima repair was performed 14 days after stent retrieval.

A retrospective analysis of the diagnostic accuracy and technical quality of frozen sections in detecting hepatobiliary lesions.

INTRODUCTION: Pathological consultation on intraoperative frozen sections plays a crucial role in the management of patients undergoing surgical therapy, and is also a key indicator for quality assurance in anatomical pathology. This study aimed to evaluate the diagnostic accuracy and technical quality of frozen sections in detecting hepatobiliary lesions with malignant potential. PATIENTS AND METHODS: A retrospective database review was performed for 1208 cases intraoperative pathology consultation who underwent hepatobiliary lesions resection at our institution from 2016 to 2020. The intraoperative consultation cases during a 5-year period were reviewed and analyzed, including the measurement of the diagnostic accuracy and turnaround time of frozen sections, the reasons for discrepancies, and the rates of discordance and deferral. RESULTS: In this study, we confirmed that the overall accuracy, sensitivity and specificity were 95.3 %, 96.3 % and 96.6 %, respectively, in distinguishing benign from malignant lesions. The rates of deferred and discordant diagnoses were 2.57 % and 2.2 %, respectively. The overall frozen section turnaround time was 22.1 min. The most common cause of deferred and discordant was poor section quality, the lesion of bile duct margin on the frozen section, misinterpretation of difficult and complicated cases, etc. CONCLUSIONS: This study confirms that the intraoperative frozen sections can serve as a rapid, accurate and robust method for the pathological diagnosis of suspected hepatobiliary lesions. However, it should be noted that some poor technical problems, pathological assessment of tumor margin and difficult cases are the most frequently causes of deferred and discordant interpretations.

A narrative review of research advances in hypoxic pulmonary hypertension.

Background and Objective: Hypoxic pulmonary hypertension (HPH) is a pathological syndrome characterized by pulmonary vasoconstriction and pulmonary vascular remodeling caused by hypoxia, which eventually leads to right heart failure or death. There are 2 stages of onset of HPH: hypoxic pulmonary vasoconstriction (HPV) and hypoxic pulmonary vascular remodeling (HPVR). It is an important pathophysiological link in the pathogenesis of chronic obstructive pulmonary disease (COPD) and chronic mountain sickness (CMS), and its severity is closely related to the course and prognosis of COPD and CMS. However, there is a lack of systematic review on the diagnosis, pathogenesis and treatment of HPH. The objective of this paper is to review the diagnosis, pathogenesis, treatment of HPH. Methods: In this paper, the method of literature review is adopted to obtain the information about HPH. Based on the literature, comprehensive and systematic review is made. The diagnosis, pathogenesis, treatment of HPH are summarized. Key Content and Findings: Right heart catheterization is the gold standard for diagnosing HPH. Hypoxia-inducible factor, oxidative stress, metal metabolism, ion channel, inflammatory cytokines, cell apoptosis and vascular factors are the main pathogenesis of HPH. The treatment of HPH includes long-term oxygen therapy, statins, prostaglandins, phosphodiesterase inhibitor and ET receptor antagonists. Conclusions: Although great progress has been made in the pathophysiology and molecular biology of HPH, it is still unclear which factors play a leading role in the pathogenesis of HPH, and no breakthrough has been made in the treatment of HPH. It is believed that the specific mechanism will be revealed as the research continues, and earlier diagnosis and the development of more effective targeted drugs will be the focus of future research.

A Novel Pathological Scoring System for Hepatic Cirrhosis with Hepatocellular Carcinoma.

PURPOSE: This study aimed to propose an effective quantitative pathological scoring system and to establish nomogram to assess the stage of cirrhosis and predict postoperative survival of hepatocellular carcinoma (HCC) with cirrhosis patients after hepatectomy. METHODS: The scoring system was based on a retrospective study on 163 patients who underwent partial hepatectomy for HCC with cirrhosis. The clinicopathological and follow-up data of 163 HCC with cirrhosis patients who underwent hepatectomy in our hospital from 2010 to 2014 were retrospectively reviewed. A scoring system was established based on the total value of independent predictive factors of cirrhosis. The results were validated using 97 patients operated on from 2011 to 2015 at the same institution. Nomogram was then formulated using a multivariate Cox proportional hazards model to analyze. RESULTS: The scoring system was ultimately composed of 4 independent predictive factors and was divided into 3 levels. The new cirrhosis system score strongly correlated with Child-Pugh score (r=0.8058, P<0.0001) 3 months after surgery; higher cirrhosis system scores predicted poorer liver function and stronger liver damage 3 months after surgery. Then, a four-factor nomogram for survival prediction was established. The concordance indices were 0.79 for the survival-prediction nomogram. The calibration curves showed good agreement between predictions by the nomogram and actual survival outcomes. CONCLUSION: This new scoring system of cirrhosis can help us predict the liver function and liver injury 3 months after surgery, and the nomogram enabled accurate predictions of risk of overall survival in patients of HCC with cirrhosis after hepatectomy.

Prognostic Nomogram for Sorafenib Benefit in Hepatitis B Virus-Related Hepatocellular Carcinoma After Partial Hepatectomy.

BACKGROUND: Predicting the long-term prognosis of individuals who experienced sorafenib treatment following partial hepatectomy due to hepatitis B virus (HBV) related hepatocellular carcinoma (HCC) is difficult. This work aims to create an effective prognostic nomogram for HBV related HCC patients who are receiving sorafenib treatment as adjuvant therapy after surgery. METHODS: A total of 233 HBV-related HCC patients treated with or without sorafenib following partial hepatectomy at the Eastern Hepatobiliary Surgery Hospital from 2008 to 2013 were matched with propensity score matching analysis. The optimal cut-off point of the overall survival (OS) factor level was determined by x-tile. The selection of indicators was based on clinical findings. The Cox regression model with an interaction term was employed for evaluating the predictive value. Using a multivariate Cox proportional hazards model, a nomogram was subsequently formulated to analyze 111 patients treated with sorafenib. The nomogram's discriminative ability and predictive accuracy were determined using the concordance index (C-index), calibration, and ROC curve. RESULTS: The matched sorafenib cohort of 111 patients and control cohort of 118 patients were analyzed. Subgroup analysis revealed that low GPC3, pERK, pAKT, serum AFP levels, without MVI, under 50 years old, male, TNM stage I/II and BCLC stage 0/A were significantly associated with a better OS in patients subjected to sorafenib treatment compared to those without sorafenib treatment after surgery. Multivariate analysis of the sorafenib cohort revealed GPC3, pERK, pAKT, serum AST, and BCLC stage as independent factors for OS, and all were included in the nomogram. The survival probability based on the calibration curve showed that the prediction of the nomogram was in good agreement with the actual observation. The C-index of the nomogram for predicting survival was 0.73(95% CI, 0.67-0.78). The area under the ROC curve (AUC) for the nomogram to predict the survival for 1, 3, and 5-year was 0.726, 0.816, and 0.823, respectively. CONCLUSION: This proposed nomogram shows the potential to make a precise prediction regarding the prognosis of HBV-related HCC patients and may help to stratify patients for personalized therapy following partial hepatectomy.

KRAS mutation and immunohistochemical profile in intraductal papillary neoplasm of the intrahepatic bile ducts.

Intraductal papillary neoplasm of bile duct (IPNB) is characterized by a spectrum of diseases ranging from low-grade intraepithelial neoplasia to invasive carcinoma. In the present study, we aimed to investigate immunophenotypic features and KRAS mutations in relation to pathological subtypes and grades in Chinese patients with IPNBs. A total of 46 patients with IPNBs and 11 invasive adenocarcinomas arising in IPNBs (invasive IPNBs) were enrolled and clinicopathological data were analyzed. It was found that CK7 was expressed in 42 of the 46 neoplastic lesions. HepPar1 was expressed in 11 of the 46 noninvasive IPNBs, but not in invasive IPNBs. Additionally, CK19 was frequently expressed in both noninvasive IPNBs and invasive IPNBs. The intestinal-type IPNBs had a significantly higher percentage of MUC2 expression relative to the pancreaticobiliary (P=0.015) and gastric-type IPNBs (P<0.001). High-grade IPNBs and invasive IPNBs showed increased expression of cyclin D1, Ki-67, p53, mCEA, and CA19-9. The rate of KRAS mutation was significantly higher in high-grade IPNBs (P=0.001) and invasive IPNBs (P=0.006) than that in low- to intermediate-grade IPNBs. Additionally, KRAS mutation was significantly associated with tumor size, and Ki-67 expression. In conclusion, the expression of cyclin D, Ki-67, p53, mCEA and CA19-9 and KRAS mutation status are significantly correlated with histological grades of IPNBs.

SUOX is a promising diagnostic and prognostic biomarker for hepatocellular carcinoma.

BACKGROUND & AIMS: To investigate diagnostic and prognostic values of sulfite oxidase (SUOX) in patients with hepatocellular carcinoma (HCC) who underwent curative resection. METHODS: We investigated immunohistochemically the expression dynamics of SUOX, aldo-ketoreductase family 1 member B10 (AKR1B10) and CD34 at different stages of HCC. The differential diagnostic performance of three markers or their combinations in high-grade dysplastic nodules (HGDNs) and well-differentiated small HCC (WD-sHCC) were investigated by logistic regression models and validated in an independent testing set. Overall survival (OS) and time to recurrence (TTR) were evaluated in 300 patients with HCC as the testing cohort, and validated in 198 patients with HCC. RESULTS: SUOX was decreased and AKR1B10 and CD34 were increased with the stepwise progression of hepatocarcinogenesis. For differential diagnosis of WD-sHCC from HGDNs, the sensitivity and specificity of the SUOX+AKR1B10+CD34 combination for WD-sHCC detection were 93.8% and 95.2%, respectively, and overall accuracy was much higher than any of the three individual markers and two marker combinations. In addition, SUOX, but not AKR1B10 and CD34, was an independent prognostic factor for OS and TTR, and showed better correlation with OS and TTR if combined with serum α-fetoprotein (AFP) for both the testing and validation cohorts. CONCLUSIONS: SUOX+AKR1B10+CD34 combination could make a substantial contribution to hepatic immunopathological diagnosis to distinguish WD-sHCC from HGDNs. Meanwhile, SUOX combined with serum AFP may predict postoperative outcome and tumor recurrence risk.

A novel panel of biomarkers in distinction of small well-differentiated HCC from dysplastic nodules and outcome values.

BACKGROUND: Differential diagnosis of high-grade dysplastic nodules (HGDN) and well-differentiated hepatocellular carcinoma (WDHCC) represents a challenge to experienced hepatic clinicians, radiologists and hepatopathologists. METHODS: The expression profiles of aminoacylase-1 (ACY1), sequestosome-1 (SQSTM1) and glypican-3 (GPC3) in low-grade dysplastic nodules (LGDN), HGDN and WDHCC were assessed by immunohistochemistry. The differential diagnostic performances of these three markers alone and in combination for HGDN and WDHCC were investigated by logistic regression models (HGDN = 21; WDHCC = 32) and validated in an independent test set (HGDN, n = 21; WDHCC n = 24). Postoperative overall survival and time to recurrence were evaluated by univariate and multivariate analyses in an independent set of 500 patients. RESULTS: ACY1, SQSTM1 and GPC3 were differentially expressed in each group. For the differential diagnosis of WDHCC from HGDN, the sensitivity and specificity of the combination of ACY1 + SQSTM1 + GPC3 for detecting WDHCC were 93.8% and 95.2% respectively in the training set, which were higher than any of the three two-marker combinations. The validities of the four diagnostic models were further confirmed in an independent test set, and corresponding good sensitivity and specificity were observed. Interestingly, GPC3 expression in HCC tissues combined with serum α-fetoprotein (AFP) was found to be an independent predictor for overall survival and time to recurrence. CONCLUSIONS: ACY1 + SQSTM1 + GPC3 combination represents a potentially valuable biomarker for distinguishing between WDHCC and HGDN using immunohistochemistry. Meanwhile, low GPC3 staining combined with positive serum AFP may play a practical role in predicting poor postoperative outcome and high tumor recurrence risk.

Using loss of heterozygosity of microsatellites to distinguish high-grade dysplastic nodule from early minute hepatocellular carcinoma.

BACKGROUND: It is practical significant to seek new applicable adjuvant diagnostic biomarkers to differentiate high-grade dysplastic nodule (HGDN) from well-differentiated minute hepatocellular carcinoma (w-MHCC) due to their closely overlapping morphology. METHODS: In the present study, by using microdissection-based paraffin-embedded tissues, loss of heterozygosity (LOH) patterns of a panel of 22 microsatellite (MS) markers was examined in 8 HGDN, 14 w-MHCC (≤1 cm) and 35 larger HCC (LHCC, >1 cm). RESULTS: The results revealed a stepwise increasing fractional allelic loss from HGDN, w-MHCC and LHCC (0.166±0.141, 0.377±0.198, 0.471±0.264, respectively, P=0.005). Loci-specific analyses showed that LOH on D4S415 (66.7% vs 0.0%, P=0.04), D1S507 (50.0% vs 0.0%, P=0.098), and D9S1752 (50.0% vs 0.0%, P=0.33) occurred more frequently than 50% in w-MHCC, but not in HGDN. On the other hand, LOH on D17S960, D17S1796 and D9S1749 occurred in HGDN, but not in w-MHCC. When compared with w-MHCC, LHCC had a higher LOH frequency on D17S720 (73.9% vs 36.4%, P=0.04), D17S960 (68.8% vs 0.0%, P=0.03) and D17S1796 (81.8% vs 0.0%, P=0.01). CONCLUSIONS: The present study suggests MS-LOH is a simple and specific assay for routinely diagnostic pathology. We recommend that D4S415, D1S507, D9S1752, D17S960, D17S1796 and D9S1749 can be used as the first-line markers for differential diagnosis between HGDN and w-MHCC, and D9S1748, D17S921 and D17S520 with a LOH frequency of 40%-50% in w-MHCC, but netative in HGDN, can be regarded as the second-line candidate markers.

Angiogenesis and lymphangiogenesis in sporadic hepatic angiomyolipoma.

Angiogenesis and lymphangiogenesis are critical processes for tumor growth, invasion, and metastasis. The present study aimed to investigate the distribution and clinical significance of angiogenesis and lymphangiogenesis in hepatic angiomyolipoma (AML). We performed immunohistochemical staining for endothelial cell markers (CD34 and podoplanin) on 80 cases of sporadic hepatic AMLs. Microvessel density (MVD) and lymphatic vessel density (LVD) were determined in intratumoral and peritumoral regions and adjacent non-tumorous liver tissues. All hepatic AMLs showed positive staining for CD34 and podoplanin. Intratumoral and peritumoral MVDs and LVDs were significantly higher than those in adjacent liver tissues (P<0.001). No statistical difference in both MVD and LVD was found between intratumoral and peritumoral areas. Large tumors (>5cm) had a significantly increased MVD and LVD as compared with smaller tumors. A significant positive correlation was found between average LVDs and MVDs (r=0.567, P<0.001), and LVDs were a relatively lower event as compared with MVDs. Double immunostaining revealed that no neoplastic cells positive for HMB-45, an antibody reacting with melanosome-associated antigen, were concurrently immunoreactive for endothelial cell markers. In conclusion, intratumoral and peritumoral angiogenesis and lymphangiogenesis commonly occur in hepatic AMLs, thus representing potential therapeutic targets for this disease.

Pathobiological features of small hepatocellular carcinoma: correlation between tumor size and biological behavior.

PURPOSE: Increasing evidence has suggested that tumor size is one of the independent prognostic factors of patients with hepatocellular carcinoma (HCC). However, the criteria used to determine when HCC should be classified as small remain controversial. Our objective was to evaluate the relationship between the size of HCC and its clinicopathological features. METHODS: A retrospective study on 618 patients who underwent partial hepatectomy for solitary HCC was performed. These patients were divided into Groups 1-5 according to the tumor diameter: ≤ 1, 1.1-2, 2.1-3, 3.1-5 and >5 cm, respectively. The clinicopathological variables of the patients in each group were compared statistically. RESULTS: Except for the microHCC (≤ 1 cm) which differed significantly from the other four groups in the clinicopathological variables, almost no differences existed among HCC ranging from 1 to 3 cm, or HCCs > 3 cm. If ≤ 3 cm was used as the cut-off point for small HCC (SHCC), and >3 cm for large HCC (LHCC), significant differences (P < 0.05-0.01) were observed between SHCC and LHCC in: histological grades I-II (48.0 vs. 19.4 %), capsular invasion (15.4 vs. 36.3%), tumor thrombi (6.9 vs. 23.5%), satellite nodules (12.3 vs. 35.5%), noninvasive growth patterns (69.6 vs. 25.4%), the overall survival (OS, 119.6 ± 34.7 vs. 68.5 ± 6.6 months), and the recurrence-free survival (RFS, 67.0 ± 16.7 vs. 29.5 ± 3.2 months). Multivariate Cox regression analyses show that tumor size >3 cm was one of the independent prognostic factors for both OS and RFS. CONCLUSIONS: The 3 cm cutoff seems to best determine the biological behavior and clinical prognosis of patients undergoing partial hepatectomy for early stage HCC. Overall, HCC smaller than 3 cm in diameter was closely related with a better prognosis which reflected the relatively benign pathobiological features at an early developmental stage. As HCC > 3 cm exhibited a tendency towards more aggressive behavior, we suggest that HCC ≤ 3 cm in diameter should be used as a critical size of SHCC at which curative treatment achieves better long-term survivals.

[Biopathological characteristics of hilar cholangiocarcinoma and the clinical significance].

OBJECTIVE: To approach the biopathological features of hilar cholangiocarcinoma and surgical pathological factors which influence the long-term survivals of patients with hilar cholangiocarcinoma. METHODS: A systemic and retrospective multi-parameter analysis was performed on 205 patients of hilar cholangiocarcinoma who received surgical treatments and had complete clinicopathological data as well as follow-up results during a ten-year-period from April 1998 to April 2008. The single factor analysis was performed on age, sex, content of pre-operative serum CA19-9, Child-pugh grading, TNM classification, operation pattern, resection margin status of bile duct, vascular invasion, adjacent liver involvement, grade differentiation, infiltration-depth of bile duct, lymph node metastasis and perineural infiltration. A multivariate analysis was performed through Cox proportional hazard model. RESULTS: The single factor analysis showed that except age, sex and content of pre-operative serum CA19-9, the mainly significant factors influencing the survivals were Child-Pugh grading, TNM classification, operation pattern, bile duct margin, vascular invasion, adjacent liver involvement, grade differentiation, infiltrating-depth of bile duct, lymph node metastasis and perineural infiltration (P < 0.05). Lymph node metastasis and infiltration-depth of bile duct wall were found to be the two independent factors influencing overall survival by multivariate analysis through the Cox model. CONCLUSIONS: The most important prognostic factors influencing the long-term survivals of patients with hilar cholangiocarcinoma after operation are lymph node metastasis and depth of tumor-infiltrating of involved bile duct. During the operation, standardized evaluation through frozen section should be carried out for detection of lymph node metastasis and depth of tumor-infiltrating of involved bile ducts, which can be used as the histological indicator for surgical expansion, and could be helpful to maximize avoiding the tumor cell residues and therefore, to improve the long-term effects of surgical resection.

Expression and localization of aquaporin-1 in human cirrhotic liver.

We investigated the expression and localization of aquaporin-1 (AQP-1) in hepatitis B virus (HBV)-associated cirrhotic human liver tissues. The expression of AQP-1 at the protein and mRNA levels was analyzed by immunohistochemistry, quantitative real-time polymerase chain reaction (qPCR) and Western blotting in normal and HBV-associated cirrhotic human liver tissues. The correlation with the expression of CK19, CK7 and AQP-1 was also compared. AQP-1 staining was strongly and uniformly positive in mature bile ducts, isolated hepatic progenitor cells (HPCs) and ductular reactions. Scattered intermediate hepatocyte-like cells expressed AQP-1, which are often intimately associated with CK7 positive hepatocytes. However, the number of AQP-1+ intermediate hepatocyte-like cells was lower than that of CK7+ cells, and such positivity was rarely seen on stains for CK19. When compared with normal liver tissues, AQP-1 was overexpressed at both the mRNA and protein levels in the cirrhotic liver tissues. AQP-1 was overexpressed in the cirrhotic liver tissues. AQP-1, similar to CK19, might be a more specific and more sensitive marker than CK7 for the identification of HPCs.

Intrahepatic cholangiocarcinoma arising in multiple bile duct hamartomas: report of two cases and review of the literature.

Multiple bile duct hamartomas (BDHs)/von Meyenburg complexes, are tumor-like lesions of the liver. Malignant transformation in BDHs has been previously reported in very rare instances, and the most common tumor arising in this clinical setting is cholangiocarcinoma. Herein, we report on clinicopathological findings in two cases of cholangiocarcinoma occurring in liver with multiple BDHs. Histopathologically, multiple BDHs showed morphologic transition from clearly benign to dysplasia or carcinoma in situ, then to invasive carcinoma sequence of the biliary epithelium. The neoplastic epithelium showed positivity for cytokeratin 19, CA 19-9, and epithelial membrane antigen. Staining for Hep Par 1, alpha-fetoprotein, cytokeratin 20, and alpha1-antitrypsin was negative. All sections from the non-neoplastic liver in each specimen showed multiple BDHs. Any other clinically detectable primary tumor was not found. These two neoplasms were interpreted as a cholangiocarcinoma arising in BDHs. This suggested BDHs might be a risk factor of development of cholangiocarcinoma.

[Evaluation of immunohistochemical markers for differential diagnosis of hepatocellular carcinoma from intrahepatic cholangiocarcinoma].

OBJECTIVE: To evaluate the significance of a panel of immunohistochemical markers for distinguishing hepatocellular carcinoma (HCC) from intrahepatic cholangiocarcinoma (ICC). METHODS: Ten markers including hepatocyte paraffin 1 (Hep Par 1), polyclonal carcinoembryonic antigen (pCEA), CD34, CD10, CD105, multidrug resistance-associated protein-3 (MRP-3), cyclooxygenase-2 (COX-2), mucinous glycoprotein-1 (MUC-1), aquaporin-1 (AQP-1) and CK19 were immunohistochemically stained in the samples from 90 surgically resected HCC and 80 ICC, respectively,and the positive rate of their expression were compared statistically. RESULTS: The positive expression rates of Hep Par 1, pCEA, CD34, CD10, CD105, MRP-3, COX-2 were 85.6%, 82.2%, 87.8%, 18.9%, 8.9%, 11.1% and 48.9%, respectively, in HCC. While the positive expression rates of MUC-1, AQP-1 and CK19 were 73.8%, 65% and 92.5%, respectively, in ICC. CONCLUSION: Based on our results, Hep Par 1 and CD34 can be used as the first line markers, and pCEA and COX-2 as the second line makers, for differential diagnosis of hepatocellular carcinoma from intrahepatic cholangiocarcinoma. While MUC-1 and CK19 can be used as the first line markers and AQP-1 as the second one for the differential diagnosis of intrahepatic cholangiocarcinoma from hepatocellular carcinoma.

[A study on the association of MTHFR C677T polymorphism with genetic susceptibility to hepatocellular carcinoma].

OBJECTIVE: To evaluate the possible association of the MTHFR C677T polymorphism with genetic susceptibility to hepatocellular carcinoma (HCC) in a Chinese population. METHODS: Five hundred and eight HCC cases and 543 controls were studied. The MTHFR genotypes were determined using a PCR-based restriction fragment length polymorphism (RFLP) method. Odds ratios (ORs) for HCC and 95% confidence intervals (CIs) from unconditional logistic regression models were used to evaluate relative risks. Potential HCC risk factors were included in the logistic regression models as covariates in the multivariate analyses on genotypes and HCC risks. RESULTS: No overall significant difference in genotype distribution was found when comparing all HCC cases to controls (P = 0.258). However, a significantly increased risk of HCC was observed among T/T homozygotes (adjusted OR = 1.66, 95% CI = 1.08-2.54, P<0.05) compared to C-allele carriers (CC or CT). When stratified with sex, this trend was more prominent in females, but not in males. Females who were homozygous (T/T) for the C677T polymorphism were at a 2.64-fold (95% CI = 1.19-5.88, P<0.05) increased risk of developing HCC when compared to C-allele carriers. However in males, T/T homozygotes had a similar risk with C-allele carriers. CONCLUSION: The MTHFR C677T polymorphism may be associated with a higher HCC risk in females, but not in males in this population.

Expression of aspartyl beta-hydroxylase and its clinicopathological significance in hepatocellular carcinoma.

The human aspartyl beta-hydroxylase is a highly conserved enzyme that hydroxylates epidermal growth factor-like domains in transformation-associated proteins. The aspartyl beta-hydroxylase gene is upregulated in many human malignancies. The purpose of this study was to investigate the expression of aspartyl beta-hydroxylase in hepatocellular carcinoma. Aspartyl beta-hydroxylase mRNA levels were measured in 161 hepatocellular carcinomas and paired nontumorous liver tissues by conventional and real-time RT-PCR. Immunohistochemical staining of aspartyl beta-hydroxylase was performed using EnVision Plus system. The results showed that aspartyl beta-hydroxylase was overexpressed in 150 of 161 hepatocellular carcinomas (93%), including 45 of 48 unifocal small hepatocellular carcinomas (94%). Aspartyl beta-hydroxylase was highly expressed in hepatocellular carcinoma cells in contrast to its low level of expression in non-neoplastic liver cells. The protein expression level of aspartyl beta-hydroxylase in the hepatocellular carcinoma was parallel with the mRNA expression level (r=0.6594, P<0.0001). A significantly higher tumor aspartyl beta-hydroxylase overexpression level was associated with the presence of intrahepatic metastasis and the progression of histological grades. In conclusion, aspartyl beta-hydroxylase is overexpressed frequently in hepatocellular carcinoma, including early-stage small hepatocellular carcinoma, indicating that overexpression of aspartyl beta-hydroxylase plays a role in the development and progression of hepatocellular carcinoma.

[Association of p53 codon 72 polymorphism with genetic susceptibility to hepatocellular carcinoma in Chinese population].

OBJECTIVE: A functional single nucleotide polymorphism (SNP) at codon 72 of the gene for p53 protein (p53 R72P) has been implicated in a variety of human cancers, but the relationship between this SNP and hepatocellular carcinoma (HCC) remains obscure despite the fact that the critical role of p53 protein in HCC has been documented. This study was conducted to evaluate the link between the polymorphism with HCC stratified by chronic hepatitis B infection status in a Chinese population. METHODS: Four hundred and sixty-nine HCC cases (359 HbsAg-positive, 110 HbsAg-negative) and 567 controls (137 HbsAg-positive, 430 HbsAg-negative) were studied. The p53 genotypes were determined by a PCR based restriction fragment length polymorphism (RFLP) method. RESULTS: Overall, no correlation between HCC and the R72P genotypes was found when comparing all cases to controls or when comparing the HbsAg-positive HCC subgroup to controls. However, in HbsAg-negative subjects, the 72P allele was significantly associated with the presence of HCC (P=0.01) and had a higher risk (OR=1.69, 95% CI: 1.25-2.27) of HCC as compared to the 72R allele. By comparison to R/R homozygotes, the R/P heterozygotes and P/P homozygotes had a 1.73-fold (95% CI: 0.96-3.11) and a 3.29-fold (95% CI: 1.58-6.86) increased risk for HCC, respectively. The subjects with the 72P allele and a family history of HCC and those with the 72P allele and male gender also yielded an 11.14-fold (95% CI: 1.62-76.67) and a 9.39 fold (95% CI: 3.08-28.62) increased risk of HCC, respectively. CONCLUSION: The P allele of the p53 R72P polymorphism has an increased risk for HCC in HbsAg-negative subjects, and exerts a synergistic influence on the risk for HCC when combined with HCC family history and the male gender.